Devices and methods for treating acute kidney injury

ABSTRACT

A catheter devices/systems and methods therefrom are described herein for treating acute kidney injury, especially the contrast-induced acute kidney injury wherein the devices prevent the contrast dyes from entering into kidney and/or facilitate blood flow of kidney by said catheter system.

BACKGROUND OF THE INVENTION

Acute kidney injury (AKI), also called acute renal failure (ARF), is arapid loss of kidney function. Its causes are numerous and include lowblood volume from any cause, exposure to substances harmful to thekidney, and obstruction of the urinary tract. AKI is diagnosed on thebasis of characteristic laboratory finding, such as elevated bloodcreatinine, or inability of the kidneys to produce sufficient amounts ofurine.

Acute kidney injury is diagnosed on the basis of clinical history andlaboratory data. A diagnosis is made when there is rapid reduction inkidney function, as measured by serum creatinine, or based on a rapidreduction in urine output, termed oliguria.

For example, the use of intravascular iodinated contrast agents maycause acute kidney injury. In patients receiving intravasculariodine-containing contrast media for angiography, contrast-induced AKI(CI-AKI) is a common problem and is associated with excessivehospitalization cost, morbidity, and mortality. Clinical proceduresinvolving intravascular iodine-containing contrast media injectioninclude for example, percutaneous coronary intervention (PCI),peripheral vascular angiography and intervention, neurologicalangiography and intervention. In clinical practice, when an increase ofserum creatinine by more than 25% or 0.5 mg/dL from baseline level,without other culprit etiology for AKI within 48 to 72 hours of exposureto contrast media, the diagnosis of CI-AKI is usually made.

The management of AKI hinges on identification and treatment of theunderlying cause. In addition to treatment of the underlying disorder,management of AKI routinely includes the avoidance of substances thatare toxic to the kidneys, called nephrotoxins. These includenon-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen,iodinated contrasts such as those used for CT scans, many antibioticssuch as gentamicin, and a range of other substances.

Monitoring of renal function, by serial serum creatinine measurementsand monitoring of urine output, is routinely performed. In the hospital,insertion of urinary catheter helps monitor urine output and relievespossible bladder outlet obstruction, such as with an enlarged prostate.In prerenal AKI without fluid overload, administration of intravenousfluids is typically the first step to improve renal function. Volumestatus may be monitored with the use of a central venous catheter toavoid over- or under-replacement of fluid. Should low blood pressureprove a persistent problem in the fluid-replete patient, inotropes suchas norepinephrine and dobutamine may be given to improve cardiac outputand enhance renal perfusion. Also, while a useful pressor, there is noevidence to suggest that dopamine is of any specific benefit, and may beharmful.

The myriad causes of intrinsic AKI require specific therapies. Forexample, intrinsic AKI due to Wegener's granulomatosis may respond tosteroid medication. Toxin-induced prerenal AKI often responds todiscontinuation of the offending agent, such as aminoglycoside,penicillin, NSAIDs, or paracetamol.

If the cause is obstruction of the urinary tract, relief of theobstruction (with a nephrostomy or urinary catheter) may be necessary.

Renal replacement therapy, such as with hemodialysis, may be institutedin some cases of AKI. A systematic review of the literature in 2008shows no difference in outcomes between the use of intermittenthemodialysis and continuous venovenous hemofiltration (CVVH). Amongcritically ill patients, intensive renal replacement therapy with CVVHdoes not appear to improve outcomes compared to less intensiveintermittent hemodialysis.

SUMMARY OF THE INVENTION

In one aspect provides a device for treating or reduce the risk of acutekidney injury, comprising: a balloon catheter having at least oneballoon, at least one sensor associated with the balloon, and adisturbing means associated with the balloon, wherein the balloon withthe disturbing means generates augmented renal blood flow to avoid renalischemia and to dilute contrast media flow inside kidneys.

In another aspect provides a device for treating or reducing the risk ofacute kidney injury, comprising: a balloon catheter having at least oneballoon, at least one sensor associated with the balloon and a positionindication means wherein the balloon occlude the orifice of both sidesof renal arteries after inflation while allowing blood flow goes throughthe inflated balloon during application of the device inside abdominalaorta.

In another aspect of the present invention, there is provided a devicefor treating or reducing the risk of contrast-induced acute kidneyinjury, comprising: a catheter, a position indication means on thecatheter, and a flow disturbing means retractable into the catheterwherein the flow disturbing means is positioned at suprarenal aorta toprovide blood flow disturbance which makes a contrast media becomediluted before taking into the renal arteries carrying by a disturbedblood flow distributing back to the infra-renal aorta.

In yet another aspect provides a method for treating or reducing therisk of contrast-induced acute kidney injury comprising

inserting the catheter of claim 1 to abdominal aorta;

placing the catheter at suprarenal aorta; and

deploying the disturbing means at a position allowing the disturbingmeans to provide blood flow disturbance which makes a contrast mediabecome diluted before taking into the renal arteries.

In certain aspect of the invention, the acute kidney injury iscontrast-induced acute kidney injury. In certain embodiments, the devicecomprises a balloon catheter having a first balloon, a second balloonand at least one sensor associated with the second balloon. In someembodiments, the device comprises a balloon catheter having a firstballoon, a second balloon and at least one sensor associated with thesecond balloon. In certain embodiments, the device further comprises aside aperture for infusing normal saline or medication. In certainembodiments, the medication is a vasodilatory agent.

In certain embodiments, the vasodilatory agent is fenoldopam.

In some embodiments, the sensor is a pressure sensor. In certainembodiments, the pressure sensor measures the blood flow pressure. Insome embodiments, the sensor is a size measuring sensor. In certainembodiments, the size measuring sensor measures the size of balloon. Incertain embodiments, the device comprises two sensors. In certainembodiments, the device comprises a first sensor at upper side of thesecond balloon and a second sensor at lower side of the second balloon.In certain embodiments, the device comprises a first sensor at upperside of the second balloon and a second sensor at lower side of thesecond balloon. In certain embodiments, the sensor provides data for thecontrol unit to control the size of the first and/or second balloons.

In some embodiments, the balloon catheter further includes a guidewireand a spinning propeller. In certain embodiments, the spinning propellerspins around the central guidewire to generate directional augmentedrenal artery blood flow toward the kidney. In certain embodiments, thespinning propeller is wing shape or fin shape. In certain embodiments,the device further comprises another catheter comprising a guidewire anda spinning propeller to generate directional augmented blood flow to theother kidney. In certain embodiments, the additional catheter having aspinning propeller is functioned independently and simultaneously withthe balloon catheter to generate directional augmented blood flow toeach side of kidney.

In another aspect, a method for treating contrast-induced acute kidneyinjury is disclosed. The method comprises: inserting the devicecomprising a balloon catheter having a first balloon, a second balloon,at least one sensor to abdominal aorta; placing the balloon catheter ata position allowing the first balloon at the supra-renal aorta positionnear orifices of bilateral renal arteries; inflating the first balloonto occlude the orifice of both sides of renal arteries during theapplication of contrast media; deflating the first balloon after thecontrast media has completely employed; inflating the second balloon tothe extent not totally occlude the aorta blood flow at the location ofinfra-renal aorta near the orifice of renal arteries; deflating thesecond balloon; and infusing normal saline and/or suitable medicationvia the side aperture into the supra-renal aorta.

In some embodiments, the insertion of the device to abdominal aorta isapplied either by transfemoral artery approach or by trans-brachialartery approach or by trans-radial artery approach. In certainembodiments, the balloon catheter further includes a guidewire and aspinning propeller. In certain embodiments, the method further comprisesinserting a guidewire into renal artery. In certain embodiments, themethod further comprises inserting a spinning propeller into kidneyartery through the guidewire. In certain embodiments, the method furthercomprises spinning the spinning propeller around the central guidewireand generate directional augmented renal artery blood flow toward thekidney.

In some embodiments provide a system comprising an invention devicedescribed herein for treating acute kidney injury. In certainembodiments, the acute kidney injury is contrast-induced acute kidneyinjury. In some embodiments, the device comprises a balloon catheterhaving a first balloon, a second balloon and at least one sensorassociated with the second balloon. In certain embodiments, the devicecomprises two sensors described herein. In certain embodiments, theballoon catheter further comprises a side aperture for infusing normalsaline or medication.

INCORPORATION BY REFERENCE

All publications, patents and patent applications mentioned in thisspecification are herein incorporated by reference to the same extent asif each individual publication, patent or patent application wasspecifically and individually indicated to be incorporated by reference.

BRIEF DESCRIPTION OF THE DRAWINGS

A better understanding of the features and advantages of the presentinvention will be obtained by reference to the following detaileddescription that sets forth illustrative embodiments, in which theprinciples of the invention are used, and the accompanying drawings ofwhich:

FIG. 1 illustrates a diagram of an exemplary invention device comprisesa balloon catheter having a first balloon positioned at the supra-renalaorta position near orifices of bilateral renal arteries for treatingacute kidney injury.

FIG. 2 illustrates a diagram of an exemplary invention device fortreating acute kidney injury where first balloon is inflated to occludethe orifice of both sides of renal arteries.

FIGS. 3A TO 3D are perspective views of first balloon of the inventiondevice. FIG. 3A shows an cylinder-like inflated balloon. FIG. 3B showsthe morphology of an exemplary inflated first balloon which is“butter-fly like.” FIG. 3C shows a cross-section view of thecylinder-like inflated balloon of FIG. 3A. FIG. 3D shows a cross-sectionview of the cylinder-like inflated balloon of FIG. 3B.

FIG. 4 illustrates a diagram showing deflated first balloon 402 and asecond balloon 403 is inflated at the location of infra-renal aorta nearthe office of renal arteries.

FIG. 5 illustrates a diagram showing the vortex blood flow caused by2^(nd) balloon distension.

FIG. 6 shows that a normal saline can be infused from control box,through the catheter pore 606 into the supra-renal aorta while a secondballoon remain inflated.

FIG. 7 shows another aspect of the invention where the first balloonexerts renal artery blood flow augmentation by periodic inflation anddeflation of the first balloon.

FIG. 8 shows at the end of PCI, both first and second balloon aredeflated and normal saline as postprocedural hydration continuousinfusion of normal saline as postprocedural hydration.

FIG. 9 shows another aspect of the present invention, where a guidewireis used to guide the device for insertion of renal artery.

FIG. 10 shows that a spinning propeller is inserted to renal artery andthen spins around the central guide wire to augment renal artery bloodflow toward the kidney.

FIGS. 11A-11B show variation embodiments of a spinning propeller.

FIG. 12 illustrates an exemplary balloon type acoustic wave pump atwork.

FIGS. 13A-13B provides how the exemplary acoustic wave pump works viathe inflation and deflation of the balloon.

FIGS. 14A-14B illustrate yet another embodiment where two balloons areinvolved to create acoustic wave where the first balloon is inflated ata pre-determined size allowing the second balloon around the first oneto create acoustic wave.

FIGS. 15A-15B show computer generated blood flow simulation diagramswithout (FIG. 15A) and with (FIG. 15B) a first balloon attached with atunnel membrane. The curved lines represent the streamlines.

FIGS. 16A-16D show another aspect of the present invention where adisturbing means such as a tunnel membrane 1603A (extension from theinner rim of the first balloon) is expended/extended toward theinfra-renal aorta to further confining the renal arteries to intakeblood flow from the infra-renal aorta. FIG. 16B shows the cross sectiontop down view of FIG. 16A. FIGS. 16C and 16D show an umbrella-likedevice or a smaller second balloon as an anchor to facilitate thedeployment of the tunnel membrane.

FIGS. 17A-17C shows another embodiment of invention disturbing meanswhere a cone shaped wire device 1702 partially covered with tunnelmembrane 1703 which is deployed from catheter 1701. FIG. 17A shows aside cross section view of an exemplary wire device 1702. FIG. 17B showsthe specification of the exemplary wire device 1702 in aorta. FIG. 17Cshows that a normal saline or other suitable medicine can be applied viaan injection hole (or holes) 1708 via an infusion tube 1707 at thedistal opening 1704 or the proximal opening 1705, or combinationthereof.

FIGS. 18A-18D illustrate a variation of the embodiment of FIGS. 17A-17Cwhere a cone-cylinder shaped wire device 1802 partially covered withtunnel membrane 1803 is shown. FIG. 18A show a side cross section viewof the wire device 1802. FIG. 18B shows a top view of the wire device1802. FIG. 18C shows a bottom view of the wire device 1802. FIG. 18Dprovide an isometric view of the wire device 1802.

DETAILED DESCRIPTION OF THE INVENTION

Current treatments/managements for acute kidney injury (AKI), especiallycontrast-induced acute kidney injury are mainly supportive. They includefor example, (1) evaluating and stratifying patients with Mehran riskscore before performing percutaneous coronary intervention (PCI), (2)avoiding high-osmolar contrast media by using low-osmolar or iso-osmolarcontrast media, (3) reducing the amount of contrast media during PCI,and (4) applying intravenously isotonic sodium chloride solution orsodium bicarbonate solution hours before and after PCI, (5) avoiding useof nephrotoxic drugs (such as nonsteroidal anti-inflammatory drugs,aminoglycosides antibiotics, etc.) See Stevens 1999, Schweiger 2007,Solomon 2010. However, none of them were proven with consistent effectin preventing CI-AKI.

Provided herein are devices and systems that specifically focus onsolving the two main pathophysiological culprits of CI-AKI, which arerenal outer medulla ischemia and/or prolonged transit of contrast mediainside the kidneys.

In some embodiments, there are provided a device for treating acutekidney injury (e.g., CI-AKI) comprising a balloon catheter having atleast one balloon, at least one sensor associated with the balloon and aposition indication means wherein the balloon occlude the orifice ofboth sides of renal arteries after inflation while allowing blood flowgoes through the inflated balloon during application of the deviceinside abdominal aorta. In some embodiments, the position indicationmeans is a radio-opaque marker, or the like.

Radio opaque marker is a vital prerequisite on an increasing number ofendovascular medical devices. The value of radio opaque markers isclearly seen in visibility improvement during deployment of the device.Markers allow for improved tracking and positioning of an implantabledevice during a procedure using fluoroscopy or radiography.

In some embodiments, the device for treating CI-AKI comprising a ballooncatheter having a first balloon, a second balloon, at least one sensorassociated with the first balloon and a device position indication meanswherein the first balloon occlude the orifice of both sides of renalarteries after inflation while allowing blood flow goes through theinflated balloon.

In some embodiments, there is provided a device for treating acutekidney injury, comprising: a balloon catheter having at least oneballoon, at least one sensor associated with the balloon and a positionindication means wherein the balloon occlude the orifice of both sidesof renal arteries after inflation while allowing blood flow goes throughthe inflated balloon during application of the device inside abdominalaorta.

Referring to FIG. 1, an exemplary invention device 100 comprising aballoon catheter 101, a first balloon 102, a second balloon 103 and aradio opaque marker on the tip of the catheter 101 is shown. FIG. 1shows that the device is inserted via femoral artery and the position ofthe device is monitored via a radio-opaque marker, or the like. Thecatheter of the device can be inserted into abdominal aorta by eithertransfemoral arterial approach or by trans-brachial artery approach orby trans-radial artery approach. The tip with radio-opaque marker ispositioned to allow the first balloon at the supra-renal aorta positionnear orifices of bilateral renal arteries.

Referring to FIG. 2, a diagram is shown that the device 200 comprising acatheter 201 having a first balloon 202 positioned at the supra-renalaorta position near orifices of bilateral renal arteries and the firstballoon 202 is inflated where the inflated first balloon occlude theorifice of both sides of renal arteries so that the bolus influx ofcontrast media (or any other harmful agents during the application ofthe invention device) flowing from supra-renal aorta is prevented fromentering into renal arteries and cause subsequent toxic effect. Thesecond balloon 203 remains un-inflated.

In certain embodiments, the device comprises a balloon catheter having afirst balloon, a second balloon and at least one sensor associated withthe second balloon. In some embodiments, the device comprises a ballooncatheter having a first balloon, a second balloon and at least onesensor associated with the second balloon.

FIGS. 3A to 3D illustrate various embodiments of the first balloon. FIG.3A shows an inflated first balloon 302 positions along with andcirculates the catheter 301. The cross-section view of the inflatablefirst balloon of FIG. 3A shows a hollow area inside the balloon andoutside the catheter 301 (a donut like balloon) allowing blood to flowalong the catheter (FIG. 3B). The first balloon 302 is inflated via atleast one connection tube 304 from the catheter 301 (four tubes shown inFIG. 3B). FIG. 3C shows other variation of the morphology of inflatablefirst balloon. A bilateral inflated balloon (303 a and 303 b) connectedto each side of catheter 301 via connection tube 304 to occlude theorifices of both sides of renal arteries are shown in FIG. 3C, whichalso allows blood to flow along the catheter. FIG. 3D shows thecross-section view of the inflated first balloon of FIG. 3C (a butterflylike balloon). The butterfly like first balloon(s) are connected to thecatheter via one or more connection tube 304 (shown one connection tubeon each side of the catheter 301). In certain embodiments, the balloonhas one, two, three, four or five connection tubes 304 for connection ofthe first balloon to the catheter and for inflation/deflation means.

In some embodiments, the first balloon is donut-like after inflation. Incertain embodiment the first balloon is butterfly-like after inflation.

Referring to FIG. 4, it is shown an exemplary device 400 comprising adeflated first balloon 402 after contrast media containing blood passedby and then the second balloon 403 is inflated at the location ofinfra-renal aorta near the orifice of renal arteries.

The inflation of the second balloon 503 is to the extent not totallyoccludes the aorta blood flow. As shown in FIG. 5, in the aorta, thevortex blood flow caused by the inflated second balloon distension willfacilitate (augment) renal artery blood flow. In some embodiments, thereis at least one sensor associated with the first balloon or secondballoon for the control of inflation/deflation of either the firstand/or second balloon. In some embodiments, the sensor is a pressuresensor. In some embodiments, the sensor is a size measuring sensorrelated to the size of either the first balloon or the second balloon.As shown in FIG. 5 as a non-limited example, there are one pressuresensor 504 at lower side of the first balloon (or at the upper side ofthe second balloon) and another pressure sensor 505 at lower side of thesecond balloon.

The analysis of data from the pressure sensors can be used asinstantaneous titration of distention degree of the second balloon toprovide adequate pressure gradient, and hence adequate vortex flow intorenal arteries. In addition, the altered aorta blood flow will increasethe renal artery blood flow, due to the location proximity and thediameter of the distended the second balloon. In some embodiments, thediameter of the distended second balloon is adjustable such that thediameter of the distended balloon is not too large to totally obstructaorta blood flow and the altered aorta blood flow will not causeinadequacy of aorta blood flow at distal aorta or branches of aorta,i.e. right and left common iliac artery. Furthermore, the aorta wallwill not be injured by the balloon distension.

Also shown in FIG. 5, there is a control box 509 outside the patientbody, in connection with the balloon catheter. The control box willserve several functions: inflation and deflation of the first and secondballoons, pressure sensing and/or measurement of upper and lowerpressure sensors, normal saline titration via an included infusion pumpwith titratable infusion rate.

In some embodiments, there are two sets of pressure sensors, one at thesupra-renal aorta side of the balloon, the other at the infra-renalaorta side of the balloon. The two sensors can continuously measure thepressure and the measured data can be exhibited at the control boxoutside of the patient's body. The pressure difference between the twosensors will be exhibited on the control box. Physicians can read thepressure difference and adjust the size of balloon by way of controlbox. Or the control box can do the adjustment of size of balloonautomatically.

In some embodiments, the device for treating acute kidney injury furthercomprises a side aperture on the balloon catheter for application ofnormal saline or other medication infused from the control box, throughthe catheter into the supra-renal aorta. In some embodiments, normalsaline (or other medication) is applied via a side aperture between thefirst and second balloon. In some embodiments, normal saline (or othermedication) is applied via the tip of catheter.

As illustrated in FIG. 6, an exemplary device for treating AKIcomprising a first balloon 602, a second balloon 603 (shown inflated), afirst sensor 604, a second sensor 605 and a side aperture 606 wherenormal saline can be infused into the supra-renal aorta via the sideaperture 606. By infusion of normal saline into the supra-renal aorta,the renal artery blood flow can be further augmented. Furthermore, itavoids the direct fluid overload burden onto the heart, especially whenpatients already have congestive heart failure. For the treatment ofCI-AKI, the infusion of normal saline into the supra-renal aorta alsodilutes the concentration of contrast media in the supra-renal aorta,therefore reduces the concentration of contrast media and thus reducethe adverse effect of hyperviscosity caused by contrast media to thekidneys, after the contrast media flowing into the kidneys. In someembodiments, the infusion rate of normal saline through the sideaperture into aorta can be controlled by the control box. In someembodiments, there is a control pump inside the control box to applynormal saline via the side aperture. In some embodiments, the controlpump is in a separate unit. In some embodiments, the medication is avasodilatory agent. In certain embodiments, the vasodilatory agent isFenoldopam, or the like. In certain embodiments, the medication such asFenoldopam, or the like is infused via the side aperture for preventionand/or treatment of CI-AKI.

FIG. 7 demonstrates another variation of the invention device comprisinga balloon catheter having a first balloon 702, a second balloon 703(shown inflated), at least one sensor (shown two sensors 704 and 705)and a side aperture where the first balloon 702 can exert renal arteryblood flow augmentation by periodic inflation and deflation. As shown inFIG. 7, when the first balloon is inflated, it will not be inflated tototally occlude the orifice of renal arteries as shown in FIG. 2. Suchperiodic balloon inflation/deflation will cause blood flow into renalarteries.

Referring to FIG. 8 at the end of percutaneous coronary intervention(PCI), both the first and second balloons will be deflated and eitherremoved or remained inside aorta and normal saline will be continuouslyinfused via a side aperture 806 as postprocedural hydration.

As illustrated in FIG. 9, an exemplary device for treating AKIcomprising a catheter 901, a first balloon 902, a second balloon 903, afirst sensor 904, a second sensor 905, a side aperture 906 furtherincludes a guidewire 910. The guidewire is inserted into renal arteryvia a catheter. When guidewire is inside renal artery, the outer sheathcatheter is also inserted into renal artery.

FIG. 10 shows that a spinning propeller 1011 is inserted from outersheath catheter into renal artery through the guidewire 1010. Theexemplary unidirectional flow pump such as a spinning propeller thenspins around the central guidewire and generate directional augmentedrenal artery blood flow toward the kidney, hence achieves the goal ofaugmented renal artery flow.

FIGS. 11A and 11B show variations of the spinning propeller. Thespinning propeller in some embodiments is wing shape, fin shape, or thelike.

In some embodiments, the balloon catheter further includes a guidewireand a spinning propeller. In certain embodiments, the spinning propellerspins around the central guidewire to generate directional augmentedrenal artery blood flow toward the kidney. In certain embodiments, thespinning propeller is wing shape or fin shape. In certain embodiments,the device further comprises another catheter comprising a guidewire anda spinning propeller to generate directional augmented blood flow to theother kidney. In certain embodiments, the additional catheter having aspinning propeller is functioned independently and simultaneously withthe balloon catheter to generate directional augmented blood flow toeach side of kidney.

MEMsPump

Microelectromechanical systems (MEMS) (also written asmicro-electro-mechanical, MicroElectroMechanical or microelectronic andmicroelectromechanical systems and the related micromechatronics) is thetechnology of very small devices. MEMS are made up of components between1 to 100 micrometres in size (i.e. 0.001 to 0.1 mm), and MEMS devicesgenerally range in size from 20 micrometres (20 millionths of a metre)to a millimetre (i.e. 0.02 to 1.0 mm). They usually consist of a centralunit that processes data (the microprocessor) and several componentsthat interact with the surroundings such as microsensors. Thefabrication of MEMS evolved from the process technology in semiconductordevice fabrication, i.e. the basic techniques are deposition of materiallayers, patterning by photolithography and etching to produce therequired shapes. Patterning in MEMS is the transfer of a pattern into amaterial. Typically, the most common MEMS pump have a patternedvibrating chamber connected a flow inlet and an outlet. This chamber isusually driven by piezoelectricity, such as the product of Bartels(http://www.micro-components.com). The vibration can also be driven bypneumatics (see e.g., Chun-Wei Huang, Song-Bin Huang, and Gwo-Bin Lee,“Pneumatic micropumps with serially connected actuation chambers,”Journal of Micromechanics and Microengineering, 16(11), 2265, 2006),electrostatics (e.g., Tarik Bourouina, Alain Bossebuf, and Jean-PaulGranschamp, “Design and simulation of an electrostatic micropump fordrug-delivery applications,” Journal of Micromechanics andMicroengineering, 7(3), 186, 1997), or electrothermal mechanism (RumiZhang, Graham A. Jullien, and Colin Dalton, “Study on an alternatingcurrent electrothermal micropump for microneedle-based fluid deliverysystems,” Journal of Applied Physics, 114, 024701, 2013).

Acoustic Wave Pump

Acoustic Streaming is ideal for microfluidic systems because it arisesfrom viscous forces which are the dominant forces in low Reynolds flowsand which usually hamper microfluidic systems. Also, streaming forcescales favorably as the size of the channel, conveying a fluid throughwhich an acoustic wave propagates, decreases. Because of acousticattenuation via viscous losses, a gradient in the Reynolds stresses ismanifest as a body force that drives acoustic streaming as well asstreaming from Lagrangian components of the flow. For more informationon the basic theory of acoustic streaming please seeEngineering_Acoustics/Acoustic streaming. When applied to microchannels,the principles of acoustic streaming typical include bulk viscouseffects (dominant far from the boundary layer, though driven by boundarylayer streaming), as well as streaming inside the boundary layer. In amicromachined channel, the dimensions of the channels are on the orderof boundary layer thickness, so both the inner and outer boundary layerstreaming need to be evaluated to have a precise prediction for flowrates in acoustic streaming micropumps The derivation that follows isfor a circular channel of constant cross section assuming that theincident acoustic wave is planar and bound within the channel filledwith a viscous fluid. The acoustic wave has a known amplitude and fillsthe entire cross-section and there is no reflections of the acousticwave. The walls of the channel are also assumed to be rigid. This isimportant, because rigid boundary interaction results in boundary layerstreaming that dominates the flow profile for channels on the order ofor smaller than the boundary layer associated with viscous flow in apipe. This derivation follows from the streaming equations developed byNyborg who starts with the compressible continuity equation for aNewtonian fluid and the Navier-Stokes and dynamic equations to get anexpression for the net force per unit volume. Eckart uses the method ofsuccessive approximations with the pressure, velocity, and densityexpressed as the sum of first and second order terms. Since the firstorder terms account for the oscillating portion of the variables, thetime average is zero. The second order terms arise from streaming andare time independent contributions to velocity, density, and pressure.These non-linear effects due to viscous attenuation of the acousticradiation in the fluid are responsible for a constant streamingvelocity.

Acoustic wave devices such as surface acoustic wave (SAW) devices havebeen in commercial use for more than 60 years, with their mainapplications in communications (e.g., filters and oscillators in mobilephone or televisions). Various microfluidic acoustic wave pumps havebeen developed to control, manipulate, and mix the minute amount ofliquid in microliter to picoliter volumes, including devices based onmechanical moving parts (such as oscillating membranes), electric fieldsapplied to liquids, magnetic fields applied to fluids or inducing phasechanges in fluids. The surface acoustic wave in some instances isgenerated by applying a if signal to a set of interdigitated transducers(IDTs) which lie on top of a piezoelectric material. When the frequency,f, of the rf signal is equal to Vs/p, where Vs is the acoustic velocityof the substrate/piezoelectric system and p is the periodic spacing ofthe IDT electrodes, then constructive interference occurs and an intenseacoustic wave is generated which travels through the piezoelectricsubstrate. The mode of the acoustic wave is determined by thecrystallographic orientation of the piezoelectric material and, in thecase of devices using a thin film piezoelectric, the thickness of thepiezoelectric layer. For microfluidic applications, a component of theacoustic wave is required in the direction of propagation, and the so-called Rayleigh mode is commonly employed in which an individual atomperforms elliptical motion in the plane perpendicular to the surface andparallel to the direction of propagation. However, the excessive dampingof the Rayleigh mode by the liquid means that this mode is considered tobe unsuitable for sensing applications. The coupling of the acousticwave into liquid on the surface of the SAW device, which is required forpumping or mixing, occurs through the excited longitudinal wavespropagating into the liquid at an angle called the Rayleigh angle,following the Snell law of diffraction as below: The Rayleigh angle,theta, is defined by

$v = {\sin^{- 1}\left( \frac{v_{L}}{v_{S}} \right)}$

where V_(L) is the velocity of the longitudinal wave in the liquid.However, the energy and the momentum of the longitudinal wave radiatedinto the liquid are quite useful for liquid pumping and mixing (X. Du etal, “ZnO film based surface acoustic wave micro-pump,” Journal ofPhysics: Conference Series, 76(1), 012047, 2007). A skilled person inthe art could prepare and employ an acoustic wave pump based on thetheory provided above.

As illustrated in FIG. 12, an exemplary acoustic wave pump is employednear renal arteries. The exemplary acoustic wave pump include aninflatable first balloon where at its deflated stage, the blood streamcan flow through freely. The first balloon then inflates and deflates ina preset adjustable frequency to create acoustic wave which forces theblood flow to enter renal arteries (see FIGS. 13A-13B). In someembodiments, the balloon is fully inflated where its outer circumferencecontacts the aorta wall which defines as 100% inflation. In someembodiments, the balloon is inflated 90%, 80%, 70%, 60%, 50%,40%, 30%.In some embodiments, the balloon is inflated 99.9% to 10%, 80% to 20%,70% to 30%. In some embodiments, the shape of the balloon varies fromsphere, cylinder, donut-like to sausage-like shape. Theinflation-depletion period (P) is adjustable. FIGS. 14A-14B illustrateyet another embodiment where two balloons are involved to createacoustic wave. FIG. 14A shows a second balloon inflated and deflatedaround a first balloon that is inflated to a pre-determined size. Theinflated first balloon induces a consistent pressure increase in aortato facilitate blood flowing into renal arteries. The wave frequency canbe adjusted so the donut-like second balloon can create desire bloodflow toward renal arteries. The first and second balloons are fullyinflated in each own inflation state. The full inflation is to preventunexpected balloon deformation due to aorta blood flow. In certainembodiments, the first balloon and the disturbing means is coated withcontrast-media absorber to remove contrast media from the blood so thatit can dilute the contrast media concentration, further reducing theharm by contrast media to kidneys.

In some embodiments, the balloon catheter further includes a guidewireand a flow augmentation means to generate directional augmented renalartery blood flow toward the kidney. For example, the flow augmentationmeans comprise a spinning propeller, a micro-electro-mechanical (MEM)micropump, an acoustic wave pump, or the like. In some embodiments, theflow augmentation means is a spinner propeller. In some embodiments, theflow augmentation means is a micro-electro-mechanical (MEM) micropump.In some embodiments, the flow augmentation means is an acoustic wavepump.

Referring to FIGS. 15A and 15B, the computer generated blood flowsimulation diagrams without (15A) and with (15B) a first balloon (e.g.,a donut-like balloon after inflation) attached with a tunnel membraneare shown. The curved lines represent the streamlines. Upon inflation,the first balloon is inflated to form a hollow cylinder. The outer wallof the inflated balloon is in contact with the aorta wall. The inflatedballoon exerts its function by the following mechanism. The stagnationregion, where the blood flow rate is zero, is formed adjacent to theupper wall of the inflated balloon as the blood flow is in laminarregime. As the blood flows through the balloon hole, a new boundarylayer along the sidewall of the balloon hole is generated so that theblood flow is focused at the very central part of aorta. As a result,the blood flow in periphery part of aorta will be detoured to morecentral part of aorta so that the bolus influx of contrast media flowingfrom supra-renal aorta can be retarded into renal artery orifice. Hencethe subsequent toxic effect by contrast medium to kidneys can bereduced. The flow field in aorta without and with the invention can becompared in FIGS. 15A and 15B, respectively.

The streamlines, represented by the curved lines in FIGS. 15A and 15B,indicate the routes of sampling blood mass flow from the supra-renalaorta. Comparing to FIG. 15A, the simulation diagram in FIG. 15B showsthat the streamlines curved toward the central part of the aorta rightbefore the blood flow passes through the first balloon, which provesthat the first balloon indeed cause the blood flow to the very centralpart of aorta. As shown in FIG. 15A, without the first balloon, thestreamlines go from the supra-renal aorta into the renal arteriesdirectly, indicating that the renal arteries intake blood flow directlyfrom the supra-renal aorta where the concentration of contrast media ishigh. With the first balloon in position (see FIG. 15B) some streamlinesgo from supra-renal aorta toward infra-renal aorta before entering renalarteries, indicating that the renal arteries intake blood flow from theinfra-renal aorta, where the contrast media has been diluted by theblood flow.

These results (flow field in aorta with or without the first balloon)provide guidance to design yet another embodiment where a flowdisturbing means is associated with the balloon. In some embodiments,the flow disturbing means is a tunnel membrane attached to the firstballoon adapted to fit inside an aorta wall. In some embodiments, theflow disturbing means is an umbrella-like blood flow reducing componenteither attached to the catheter or to the first balloon positioned aboveor below renal arteries (suprarenal or infrarenal aorta areas). In someembodiments, the flow disturbing means is an umbrella-like blood flowreducing component attached to the catheter positioned at suprarenalaorta. A skilled person in the art would readily recognize any similarshapes, structures, or functions as to an umbrella-like blood flowreducing component. Without the flow disturbing means, the renalarteries intake blood directly from the supra-renal aorta where highconcentration of contrast media is contained, as shown in FIG. 15A. Whenthe disturbing means (with or without the first balloon) is applied (asshown in FIG. 15B), the renal arteries intake blood from the infra-renalaorta where the concentration of contrast media reduced. The curvedlines inside the tube in FIGS. 15A and 15B represent the streamlines ofblood flow. In FIG. 15B, contrast media goes to the infra-renal aortawith the disturbed blood flow and is hence diluted before in-taken intothe renal arteries.

The flow disturbing means is any device that can disturb blood flowresulting to a lesser renal arteries blood intake from the infra-renalaorta. Based on the practice of the present invention, a skilled personin the art can readily apply any similar device of FIG. 16A, 16C, 16D,17A, 17C, or the like.

As illustrated in FIG. 16A, a first balloon 1602 with a disturbing means(e.g., a tunnel membrane 1603A) is shown. FIG. 16B is a cross sectionview from top of FIG. 16A where at least one connection tube 1604 fromthe catheter 1601 is shown. The cross sectional view of the 1^(st)balloon showed a halo area inside the balloon, so that the halo area canprovide passage of aorta blood flow from supra-renal aorta toinfra-renal aorta. One variation of the morphology of the first balloonwith a disturbing means is to have a second balloon attached to thetunnel membrane (e.g., as shown in FIG. 16D). The first balloon expectedto locate at supra-renal aorta is larger in diameter and it can beattached to the aorta wall, where as the other balloon is smaller indiameter providing drag to deploy the tunnel membrane. In someembodiments, the first balloon does not require to be attached to theaorta wall, leaving small space around the first balloon allowing bloodseeping through. FIG. 16C yet illustrates another embodiment of thedisturbing means where an umbrella-like blood flow reducing component1603B is shown. While in the insertion mode, the umbrella-like bloodflow reducing component 1603B is folded allowing free flow of bloodstream. Once the device is at position where the disturbing means isnear and below the renal arteries, the umbrella-like blood flow reducingcomponent 1603B is unfolded due the downward blood flow direction. Thecomponent may be a second balloon 1605 attached to the tunnel membrane(see FIG. 16D). The disturbing means (e.g., a tunnel membrane, anumbrella-like blood flow reducing component, or the like) is made ofmaterial with flexibility. In some embodiments, they are made of softplastics. In some embodiments, they are made of semi-soft plastics. Inother embodiments, they are made of metal with the flexibility charactersuch as metal wire. The tunnel membrane, in some embodiments, is aflexible film such as polytetrafluoroethene, expandedpolytetrafluoroethene, silicone rubber, polyurethane, poly(ethyleneterephthalate), polyethylene, polyether ether ketone (PEEK), polyetherblock amide (PEBA), or the like.

In some embodiments, the infra-renal side of the balloon or thedisturbing means (such as infra-renal tunnel membrane) can inject salinevia injection hole into the aorta to dilute the contrast media before itflows into the renal arteries. The injection holes, in some embodiments,are located at the first balloon. The injection holes, in someembodiments, are located at catheter near the first balloon. Theinjection holes may be part of the balloon or the catheter. In someembodiments, the injection holes are located at an infusion tube. Thematerial of the such infusion tube, in some embodiments, is selectedfrom the group consisting of teflon, polyoxymethylene copolymer,polyimides, polycarbonate, polyetherimide, polyetheretherketone,polyethylene, polylactic acid, polylactide acid, polystyrene,polyurethane, PVC, thermoplastic elastomer, and combinations thereof,and the like.

As illustrated in FIG. 17A, which provides yet another embodiment of theflow disturbing means, is a cone shaped wire device 1702 partiallycovered with tunnel membrane 1703 which is deployed from catheter 1701.FIG. 17B provides an exemplary specification of the cone shaped wiredevice 1702 of FIG. 17A where the diameter of the distal opening 1704 isabout 3 to 3.2 cm or about 3.0 cm. Thus the outer rim of the wire device1702 is either tightly fitted inside the aorta (of e.g., 3.0 to 3.2 cmdiameter) or loosely situated with little space allowing blood seepingthrough. The diameter of the distal opening 1704 is based on variousdiameters of an aorta (typically from about 5 cm to about 2 cm) in thepatients where the device is deployed. In some embodiments, the distalopening has a diameter of about 5 cm to about 1.5 cm; in someembodiments, the distal opening has a diameter of about 4.5 cm to about1.7 cm; in some embodiments, the distal opening has a diameter of about4 cm to about 1.8 cm; about 3.5 cm to about 1.8 cm; or about 3 cm toabout 2.0 cm. A tunnel membrane 1703 is covered from the edge of thedistal opening 1704 to the proximal opening 1705 of the wire device. Theheight (1706, see FIG. 17B, where is the distance of blood flowingthrough) of the tunnel membrane in some embodiments is about 1.5 cm toabout 4 cm, about 2 cm to about 3.5 cm, about 2.5 cm to about 3.0 cm (asshown in FIG. 11B is 3 cm). In some embodiments, the height 1706 of thetunnel membrane is about 2 cm, about 3 cm, or about 4 cm. The proximalopening 1705 allows the blood flow through with restricted speed thatcreates a disturbing of blood flow allowing that the renal arteriesintakes blood flow from the infra-renal aorta, where the contrast mediahas been diluted by the blood flow. To create such an effective bloodflow disturbing caused by a disturbing means (e.g, the device 1702), insome embodiments, the diameter of the proximal opening is aboutone-fourth to about three-fourth of the diameter of the distal opening.In some embodiments, the diameter of the proximal opening is aboutone-third of the diameter of the distal opening. For example, as shownin FIG. 17B the diameter of the bottom opening 1705 is about 1.0 cm.Relative to where the blood flowing through from the proximal opening,blood releasing height 1709 is designed to be about one-half to aboutthree times of the diameter of the proximal opening. The ratiorelationship between blood releasing height 1709 and proximal opening1705 is based on (1) how the wire device restricts blood flow whichcreates disturbance, (2) the structural strength of the wire device, and(3) the diameter relationship between the distal opening and theproximal opening.

To support such cone shaped structure, the wire device comprises wires1710 with at least 3 wires. In some embodiments, there are 4 to 24wires, 5 to 22 wires, 6 to 20 wires, 8 to 18 wires, or 10 to 16 wires.In some embodiments, there are 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14,15, 16, 17, 18, 19, or 20 wires in the wire device partially coveredwith tunnel membrane. If needed, a skilled person in the art can preparea wire device in accordance with the practice of the present inventionto any number of wires suitable to provide a disturbing means. The wiremay be any superelastic material such as nitinol.

Pseudoelasticity, sometimes called superelasticity, is an elastic(reversible) response to an applied stress, caused by a phasetransformation between the austenitic and martensitic phases of acrystal. It is exhibited in shape-memory alloys. Pseudoelasticity isfrom the reversible motion of domain boundaries during the phasetransformation, rather than just bond stretching or the introduction ofdefects in the crystal lattice (thus it is not true superelasticity butrather pseudoelasticity). Even if the domain boundaries do becomepinned, they may be reversed through heating. Thus, a superelasticmaterial may return to its previous shape (hence, shape memory) afterthe removal of even relatively high applied strains.

The shape memory effect was first observed in AuCd in 1951 and sincethen it has been observed in numerous other alloy systems. However, onlythe NiTi alloys and some copper-based alloys have so far been usedcommercially.

For example, Copper-Zinc-Aluminum (CuZnAl) was the first copper basedsuperelastic material to be commercially exploited and the alloystypically contain 15-30 wt % Zn and 3-7 wt % Al. The Copper-Aluminum, abinary alloy, has a very high transformation temperature and a thirdelement nickel is usually added to produce Copper-Aluminum-Nickel(CuAlNi). Nickel-Titanium Alloys are commercially available assuperelastic material such as nitinol. In some embodiments, thesuperelastic material comprises copper, aluminum, nickel or titanium. Incertain embodiments, the superelastic material comprises nickel ortitanium, or combination thereof. In certain embodiments, thesuperelastic material is nitinol.

Specific structures can be formed by routing wires (bending one or a fewwires and weaving into final shape) or cutting superelastic tube (lasercutting out the unwanted parts and leaving final wires in place) orcutting superelastic fleet (laser cutting out the unwanted parts andannealing the fleet into a cone shape.

Similarly, in some embodiments, the disturbing means (e.g., the wiredevice 1702) can inject saline from one or more injection hole 1708 viaan infusion tube 1707 at the distal opening 1704 or the proximal opening1705, or combination thereof into the aorta to dilute the contrast mediafurther before it flows into the renal arteries. See FIG. 17C. In someembodiments, the injection hole(s) is on the catheter, for example atthe position close to the tip of the catheter where the disturbing meansis deployed.

In some embodiments, the cone shaped wire device comprises an uppercylinder portion 1811 as illustrated in FIG. 18A. The upper cylinderportion 1811 is used to form tight contact of the device on the aortawall. This tight contact supports the device against high pressure dueto high blood flow rate. This tight contact prevents contrast media fromleaking through the contact interface (without blood seeping through).To avoid occlusion of arteries branching from supra-renal aorta by uppercylinder portion, which is about 0.5 cm apart, the height of the uppercylinder portion should not be more than 0.5 cm to avoid blocking arterybranches. The height 1806 of the distal opening to the proximal openingshould be about 1.5 cm to about 4 cm, about 2 cm to about 3.5 cm, orabout 2.5 cm to about 3.0 cm.

As illustrated in FIG. 18A (a side view), which provides yet a variationof the embodiment of FIGS. 17A-17C, a cone-cylinder shaped wire device1802 partially covered with tunnel membrane 1803 from the rim of thedistal opening 1804 to proximal opening of 1805, which is deployed fromcatheter 1801. FIG. 18B shows a top view of the wire device 1802. FIG.18C shows a bottom view of the wire device 1802. FIG. 18D provide anisometric view of the wire device 1802.

In another aspect, a method for treating contrast-induced acute kidneyinjury is disclosed. The method comprises: inserting the catheter ofclaim 1 to abdominal aorta; placing the catheter at suprarenal aorta;and deploying the disturbing means at a position allowing the disturbingmeans to provide blood flow disturbance which makes a contrast mediabecome diluted before taking into the renal arteries. In certainembodiments, the insertion of the device to abdominal aorta is appliedeither by transfemoral artery approach or by trans-branchial arteryapproach or by trans-radial artery approach. In some embodiments, theballoon catheter further includes a guidewire and a flow augmentationmeans. In some embodiments, the method further comprises infusing normalsaline and/or suitable medication from one or more injection holes (viaan infusion tube, or the catheter) into the supra-renal aorta.

In another aspect, a method for treating contrast-induced acute kidneyinjury is disclosed. The method comprises: inserting the inventiondevice comprising a balloon catheter having a first balloon, a secondballoon, at least one sensor to abdominal aorta; placing the ballooncatheter at a position allowing the first balloon at the supra-renalaorta position near orifices of bilateral renal arteries; inflating thefirst balloon to occlude the orifice of both sides of renal arteriesduring the application of contrast media; deflating the first balloonafter the contrast media has completely employed; inflating the secondballoon to the extent not totally occlude the aorta blood flow at thelocation of infra-renal aorta near the orifice of renal arteries;deflating the second balloon; and infusing normal saline and/or suitablemedication via the side aperture into the supra-renal aorta.

In some embodiments, the insertion of the device to abdominal aorta isapplied either by transfemoral arterial approach or by trans-brachialartery approach or by trans-radial artery approach. In certainembodiments, the balloon catheter further includes a guidewire and aspinning propeller. In certain embodiments, the method further comprisesinserting a guidewire into renal artery. In certain embodiments, themethod further comprises inserting a spinning propeller into kidneyartery through the guidewire. In certain embodiments, the method furthercomprises spinning the spinning propeller around the central guidewireand generate directional augmented renal artery blood flow toward thekidney.

In some embodiments provide a system comprising an invention devicedescribed herein for treating acute kidney injury. In certainembodiments, the acute kidney injury is contrast-induced acute kidneyinjury. In some embodiments, the device comprises a catheter, a positionindication means on the catheter, and a flow disturbing meansretractable into the catheter wherein the flow disturbing means ispositioned at suprarenal aorta to provide blood flow disturbance whichmakes a contrast media become diluted before taking into the renalarteries carrying by a disturbed blood flow distributing back to theinfra-renal aorta. In some embodiments, the device comprises a ballooncatheter having a first balloon, a second balloon and at least onesensor associated with the second balloon. In certain embodiments, thedevice comprises two sensors described herein. In certain embodiments,the balloon catheter further comprises a side aperture for infusingnormal saline or medication.

Although preferred embodiments of the present invention have been shownand described herein, it will be obvious to those skilled in the artthat such embodiments are provided by way of example only. Numerousvariations, changes, and substitutions will now occur to those skilledin the art without departing from the invention. It should be understoodthat various alternatives to the embodiments of the invention describedherein can be employed in practicing the invention. It is intended thatthe following claims define the scope of the invention and that methodsand structures within the scope of these claims and their equivalents becovered thereby.

1.-54. (canceled)
 55. A device for preventing acute kidney injury fromcontrast agent introduced into vasculature of a subject, the devicecomprising: a catheter shaft having a first lateral side and a secondlateral side; a first expandable member disposed on a first lateral sideof the catheter shaft; and a second expandable member disposed on asecond lateral side of the catheter shaft, wherein the first and secondexpandable members have an expanded configuration in which when advancedinto an abdominal aorta and positioned adjacent renal artery ostia ofthe subject are sized to occlude the renal artery ostia while allowingblood flow over the catheter shaft.
 56. The device of claim 55, whereinat least a portion of one or more of the catheter shaft, firstexpandable member, or second expandable member is radio-opaque.
 57. Thedevice of claim 55, wherein the first expandable member comprises afirst inflatable balloon and the second expandable member comprises asecond inflatable balloon.
 58. The device of claim 57, wherein thecatheter shaft comprises an inflation lumen to provide inflation fluidto expand the first and second inflatable balloons.
 59. The device ofclaim 58, wherein the inflation lumen is in fluid connection with one ormore of the first or second inflatable balloons through at least oneconnection tube.
 60. The device of claim 55, further comprising apressure sensor coupled to one or more of first or second expandablemembers.
 61. The device of claim 55, further comprising a size-measuringsensor coupled to one or more of first or second expandable members. 62.The device of claim 55, wherein the catheter shaft comprises an infusionport for introducing into the abdominal aorta a bolus of a contrastagent, saline, medication, or other fluid through an infusion port ofthe catheter shaft.
 63. A method of preventing acute kidney injury fromcontrast agent introduced into vasculature of a subject, the methodcomprising: positioning a catheter device in an abdominal aorta of thesubject adjacent renal artery ostia of the subject; deploying anocclusive element of the catheter device to occlude the renal arteryostia; introducing a bolus of the contrast agent into the abdominalaorta of the subject while the occlusive element is deployed to occludethe renal artery ostia, thereby preventing the contrast agent fromentering into renal arteries of the subject; and collapsing theocclusive element after the bolus of the contrast agent has beenintroduced, thereby allowing blood flow to the renal arteries to resume.64. The method of claim 63, further comprising repeating the steps ofdeploying the occlusive element to occlude the renal artery ostia,introducing the bolus of the contrast agent while the occlusive elementis deployed, and collapsing the occlusive element after the bolus of thecontrast agent has been introduced.
 65. The method of claim 63, whereinat least a portion of the catheter device is radio-opaque and furthercomprising tracking the position of the catheter device as the catheterdevice is positioned.
 66. The method of claim 63, wherein the occlusiveelement comprises at least one inflatable balloon.
 67. The method ofclaim 66, wherein the at least one inflatable balloon comprises a firstballoon and a second balloon.
 68. The method of claim 67, wherein thefirst and second inflatable balloons are disposed bilaterally withrespect to one another to occlude a first renal ostium and a secondrenal ostium, respectively, when inflated.
 69. The method of claim 67,wherein the first and second inflatable balloons are disposed about acentral shaft of the catheter device.
 70. The method of claim 67,wherein catheter device comprises at least one connection tube forconnecting one or more of the first or second inflatable balloon to aninflation fluid lumen of the catheter device, the inflation fluid lumenproviding fluid to inflate the first or second balloon.
 71. The methodof claim 67, wherein the expanded first and second balloons allow bloodflow along the catheter device.
 72. The method of claim 63, furthercomprising measuring pressure with a sensor coupled to the occlusiveelement of the catheter device.
 73. The method of claim 63, whereinpositioning the catheter device in the abdominal aorta of the subjectcomprises advancing the catheter device through one or more of a femoralartery, a brachial artery, or a radial artery.
 74. The method of claim63, further comprising introducing into the abdominal aorta the bolus ofthe contrast agent, saline, medication, or other fluid through aninfusion port of the catheter shaft.